Open AccessNLRP 10 enhances S higella ‐induced pro‐inflammatory responses
Author(s) -
Lautz Katja,
Damm Anna,
Menning Maureen,
Wenger Julia,
Adam Alexander C.,
Zigrino Paola,
Kremmer Elisabeth,
Kufer Thomas A.
Publication year - 2012
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2012.01822.x
Subject(s) - biology , shigella , shigella flexneri , microbiology and biotechnology , immunology , computational biology , salmonella , escherichia coli , genetics , bacteria , gene
Summary Members of the NLR family evolved as intracellular sensors for bacterial and viral infection. However, our knowledge on the implication of most of the human NLR proteins in innate immune responses still remains fragmentary. Here we characterized the role of human NLRP 10 in bacterial infection. Our data revealed that NLRP 10 is a cytoplasmic localized protein that positively contributes to innate immune responses induced by the invasive bacterial pathogen S higella flexneri . SiRNA ‐mediated knock‐down studies showed that NLRP 10 contributes to pro‐inflammatory cytokine release triggered by S higella in epithelial cells and primary dermal fibroblasts, by influencing p 38 and NF ‐κ B activation. This effect is dependent on the ATP ase activity of NLRP 10 and its PYD domain. Mechanistically, NLRP 10 interacts with NOD 1, a NLR that is pivotally involved in sensing of invasive microbes, and both proteins are recruited to the bacterial entry point at the plasma membrane. Moreover, NLRP 10 physically interacts with downstream components of the NOD 1 signalling pathway, such as RIP 2, TAK 1 and NEMO . Taken together, our data revealed a novel role of NLRP 10 in innate immune responses towards bacterial infection and suggest that NLRP 10 functions as a scaffold for the formation of the NOD 1– N odosome.